The discovery of single-molecule and single-nanoparticle surface-enhanced Raman scattering (SERS) has attracted considerable interest, both for fundamental studies of enhancement mechanisms and for potential applications in ultrasensitive optical detection and spectroscopy. A number of researchers have shown that the enhancement factors are as large as 1014-1015, leading to Raman scattering cross sections that are comparable to or even larger than those of fluorescent organic dyes. This enormous enhancement allows spectroscopic detection and identification of single molecules located on the surface of single nanoparticles or at the junction of two particles at room temperature. Progress has been made concerning both the structural and mechanistic aspects of single-molecule SERS, but it is still unclear how this large enhancement effect might be exploited for applications in analytical chemistry, molecular biology, or medical diagnostics. One major problem is the intrinsic interfacial nature of SERS, which requires the molecules to adsorb on roughened metal surfaces. For biological molecules such as peptides, proteins, and nucleic acids, surface-enhanced Raman data are especially difficult to obtain, hard to interpret, and nearly impossible to reproduce. Therefore, a need in the industry exists to improve SERS data for biological molecules.
The current state-of-the-art for viral diagnostic methods involves isolation and cultivation of viruses and may employ (1) an enzyme-linked immunosorbant assay (ELISA), a method that uses antibodies linked to an enzyme whose activity can be used for quantitative determination of the antigen with which it reacts, or (2) polymerase chain reaction (PCR), a method of amplifying fragments of genetic material so that they can be detected. These diagnostic methods are cumbersome, time-consuming, and ELISA has limited sensitivity.
There is, therefore, a critical need for a rapid, reproducible and highly sensitive and specific method of diagnosing viruses such as respiratory syncytial virus (RSV) that inflict substantial disease burdens on human and animal health and (not insignificantly) for other respiratory viruses that also pose a significant threat as agents for bioterrorism. The emergence of biosensing strategies that leverage nanotechnology for direct, rapid, and increased sensitivity in detection of viruses, are needed to bridge the gap between the unacceptably low sensitivity levels of current bioassays and the burgeoning need for more rapid and sensitive detection of infectious agents.
Various viruses are responsible for many common human diseases, such as colds, flu, diarrhea, chicken pox, measles, and mumps. Some viral diseases such as rabies, hemorrhagic fevers, encephalitis, polio, yellow fever, and acquired immunodeficiency syndrome (AIDS), can result in death. German measles and cytomegalovirus can cause serious abnormalities or death in unborn infants. Of the estimated 1000 to 1500 types of viruses, approximately 250 cause disease in humans. Several human viruses are also likely to be agents of cancer. The precise role of these viruses in human cancers is not well understood, and genetic and environmental factors are likely to contribute to these diseases. But because a number of viruses have been shown to cause tumors in animal models, it is probable that many viruses have a key role in human cancers.
Viruses like HIV will continue to evolve new viral genetic subtypes and circulating recombinant forms (CRF's) as virus recombination and mutation continue to occur. In addition, the current subtypes and CRFs will also continue to spread to new areas as the global epidemic continues. With HIV, recent studies have shown that different subtypes result in different rates of infection and increases in risk of death. Standard HIV diagnostics that employ serologic tests such as the enzyme-linked immunoabsorbant assay (ELISA) and Western Blot assay are not useful in HIV diagnosis in infants because of the confounding presence of maternal antibody. Nucleic acid-based assays which detect the presence of HIV viral sequences require Polymerase Chain Reaction (PCR) amplification of target DNA sequences which is time-consuming. Early HIV detection creates the possibility of access to early therapy and its potential treatment benefits. Thus, there is a need for not only fast, reliable viral detection systems but systems that can differentiate between viral strains so that antiviral therapies can be tailored for each infected individual.